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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Chem. | doi: 10.3389/fchem.2019.00381

Discovery of Potential Anti-infective Therapy Targeting Glutamine Synthetase in Staphylococcus xylosus

Wenqiang Cui1, 2, Qianwei Qu1, 2, Jinpeng Wang1, 2,  Jingwen Bai3,  Bello-Onaghise God'Spower1, 2, Yuang Li1, 2,  Yonghui Zhou1, 2, Xingru Chen1, 2, XIn Liu1, 2, Sidi Zheng1, 2, Xiaoxu Xing1, 2, NSABIMANA Eliphaz1, 2 and  Yanhua Li1, 2*
  • 1College of Veterinary Medicine, Northeast Agricultural University, China
  • 2Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Northeast Agricultural University, China
  • 3College of Science, Northeast Agricultural University, China

Glutamine synthetase (GS), which catalyzes the production of glutamine, plays essential roles for most biological growth and biofilm formation, suggesting that GS may be used as a promising target for antibacterial therapy. We asked whether a GS inhibitor could be found as an anti-infective agent of Staphylococcus xylosus (S. xylosus). Here, computational prediction followed by experimental testing was used to characterize GS. The sorafenib was finally determined through computational prediction. In vitro experiments showed that sorafenib has an inhibitory effect on the growth of S. xylosus by competitively occupying the active site of GS, and the minimum inhibitory concentration was 4 mg/L. In vivo experiments also proved that: treatment with sorafenib significantly reduced the levels of TNF-α and IL-6 in breast tissue from mice mastitis, which was further confirmed by histopathology examination. These findings indicated that sorafenib could be utilized as an anti-infective agent for the treatment of infections caused by S. xylosus.

Keywords: glutamine synthetase, molecular docking, Sorafenib, anti-infective, Mastitis

Received: 04 Mar 2019; Accepted: 10 May 2019.

Edited by:

Nino Russo, Department of Chemistry and Chemical Technologies, University of Calabria, Italy

Reviewed by:

Sixue Zhang, Southern Research Institute, United States
Francesco Ortuso, Università degli studi Magna Græcia di Catanzaro, Italy  

Copyright: © 2019 Cui, Qu, Wang, Bai, God'Spower, Li, Zhou, Chen, Liu, Zheng, Xing, Eliphaz and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Yanhua Li, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150038, Heilongjiang Province, China, liyanhua@neau.edu.cn